This project will develop new methods for imaging cocaine-induced activation in humans and in rats using functional magnetic resonance imaging (fMRI) techniques. These techniques have the potential for analyzing non-invasively both direct vascular and euphoric responses, as well as drug-dependent behavior such as craving, with unprecedented temporal and spatial resolution. However, while fMRI has been very successful in its preliminary applications of mapping primary sensory cortices, studies of sub-cortical structures have been less fruitful. Since these sub-cortical structures appear key to understanding the physiology of drug-dependent behavior, our proposed work seeks to extend fMRI imaging sequences, map generation, and analysis techniques to optimize the detection of cocaine-induced activation. These methods address the specific issues that make fMRI unique among functional neuroimaging modalities: the mixture of sequence-dependent functional weightings available, the high spatial and temporal resolution feasible, and the unique statistical characteristics of the functional MR data. By combining novel imaging and analysis techniques, we thus seek to establish functional MR imaging as a rigorous methodology for the study of drug response and drug-dependent behavior in humans.